Phosphonium salts and P-ylides

Irina L. Odinetsa

DOI: 10.1039/9781849732819-00074

1 Introduction

This chapter covers the most significant developments during 2009 in theabove area the importance of which is obvious in different fields of chem-istry ranging from medicinal chemistry, organic synthesis to material sci-ences. As the abstraction of a proton from the corresponding conjugate acidis a classical method for preparing phosphorus ylides from the corres-ponding phosphonium salts, some publications on synthesis and chemistryof P-ylides, e.g., the one-pot version of the Wittig reaction, are intimatelyconnected with that of the parent salts.

2 Phosphonium salts

2.1 Preparation

Quaternization of the corresponding phosphines with different electro-philes, being the most typical and easy to perform procedure for thepreparation of phosphonium salts, has been used for the synthesis of newsalts designed as ionic liquids, building blocks in organic synthesis or ylideprecursors for the Wittig reaction. The examples comprise alkylation ofthe known 1,12-dicarba-closo-dodecaborane phosphine by an excess oftetraethyleneglycol dihalide (bromide or iodide) in DMF solution (an inertatmosphere, 120oC) for the preparation of new water-soluble, due to thepresence of glycol chain, phosphonium salts (1) for potential use astumor-targeting agents in Boron Neutron Capture Therapy (BNCT).1

This alkylation procedure also led to the formation of a small amount ofthe corresponding dicationic salts. Even sterically crowded bulky tetra-phosphines, obtained via PH addition to divinyl ethers of glycols underfree radical conditions, could be readily quaternized using bulky elec-trophiles such as 1-(bromomethyl)naphthalene to give the salt (2) (98%

H

Ph2PO

X3

X

X = Br, I= B

O O

OO

P

P

P

P

Br Br

Br Br

(1) (2)

P

H

Fe

FeFe

BF4

(3)

aA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,Moscow, Russia

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�c The Royal Society of Chemistry 2011

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yield), capable of being involved efficiently in Wittig–type reactions.2 Inreinvestigating the chemistry of primary, secondary and tertiary ferroce-nylmethylphosphines, phosphonium salt (3) was obtained via protonationof phosphine (FcCH2)3P by HBF4(OMe2).

3

For the preparation of novel bridged and non-bridged vicinal dipho-sphonium salts (4) and (5) based on the easily available, on a multigramscale, bis(1,2-diphenylphosphino)benzene (o-dppb), Chauvin and cow-orkers used both alkylations by different electrophiles and heating of thesulfinylethyl monophosphonium salt of o-dppb in the presence of the cat-ionic complex [Rh(cod)2][PF6] (in the case of (5), R=H, n=1). The formalelectrostatic and possible van der Waals strain in these salts was comparedthrough the Pþ . . ..Pþ distances in the crystalline state.4 Easy activation ofboth C–Cl bonds of CH2Cl2 by CoCl2 and metallic Zn allowed quantitativemethylation of aromatic and aliphatic phosphines in air to afford(R3P

þMe)2(ZnCl4) species or, in the case of phosphino-substituted oxa(-thia)zolines, zwitterionic complexes (6) with a negatively chargedZnCl3 group.5 The bromide salts [R3P-P(R’)2=NSiMe3]Br [(7), R0=Me,OCH2CF3; R3P=Me3P, Et3P, nBu3P, dmpm (dmpm=dimethylpho-sphinomethane, dmpe=dimethylphosphinoethane)] of phosphine-stabil-ized phosphoranimine cations, were prepared from the direct reactionsbetween BrMe2P=NSiMe3 and Br(CF3CH2O)2P=NSiMe3 and thecorresponding tertiary phosphines R3P or diphosphines Me2P(CH2)nPMe2.The anion exchange reactions between the bromide salts and AgOTfquantitatively afforded the more stable triflate salts. Investigation of thesolution and solid-state NMR spectral properties and reactivity of thesesalts suggested the domination of form (7a) in the equilibrium.6

P

PPh Ph

Me

Ph

Me

Ph

P

PPh

Ph

PhPh

2X

X = I, BF4, OTf, PF6

2X

(4) (5)

n

RR

R = H, Men = 0, 1, 2

NE

PMePh2

ZnCl3

E = O, S

(6)

R13P P N

R

R

SiMe3

R13P P N

R

R

SiMe3

(7b)

(7a)

Chlorination of 1,2,3,4-tetracyclohexyl-cyclo-tetraphosphine by PhICl2or PCl5 in the presence of Me3SiOTf or GaCl3 provided a stepwise app-roach to salts of the first cyclo-phosphino-chlorophosphonium cations[Cy4P4Cl]

þ ((8), X=Cl) and [Cy4P4Cl2]2þ (9). The iodomonophos-

phonium derivative [Cy4P4I]þ [GaI4]

� ((8), X=I) was obtained as thetetraiodogallate salt from reaction of 1,2,3,4-tetracyclohexyl-cyclo-tetra-phosphine with I2 in the presence of GaI3. The cyclic framework of thedication in (9) dissociates in reactions with tertiary phosphines such asPMe3 or dmpe, resulting in the formation of the linear Me3P

þP(Cy)P(Cy)PþMe3] � 2GaCl4 salt or cyclic salts (10) and (11), respectively, with thesame counter ion.7 The other approach to phosphorus-enriched phospho-nium salts comprises the solvent-free consecutive insertion of thephosphenium cation [Ph2P]

þ into the P-P bonds of P4 resulting in the

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formation of the unprecedented cationic clusters [Ph2P5]þ , [Ph4P6]2

þ , and[Ph6P7]3

þ .8

PP

PP Cy

Cy

Cy

Cy XP

PP

P Cy

Cl

Cy

Cy Cl

Cy

X = I, Cl

GaX4

2GaCl4P

P

PP

PP

PMe Me

Cy

Me Me

Cy

Cy

Me Me

Me Me

2GaCl4 2GaCl4

(8) (9) (10) (11)

Furthermore, functionalization of P4 using the cationic bifunctionalLewis acid [DippNP]2

2þ (Dipp=2,6-iPr2-C6H3), obtained by treatmentof cyclo-1,3-diphospha-2,4-diazane [DippNPCl]2 with GaCl3 in C6H5F,enabled the preparation of novel mono- and dicationic phosphorus richclusters (12)[GaCl4] �C6H5F and (13)[Ga2Cl7]2. A single-crystal X-ray studyof [12][GaCl4] �C6H5F unambiguously confirmed the insertion of the cyclicphosphenium cation [DippNP]2

2þ into one of the P-P bonds of P4.9

NP

NP Cl

P

Dipp

Dipp

PPP

NP

NP

PP

Dipp

Dipp

PP P

PPP Ph3P

O

N OBr

(12) )41()31(

The approaches to phosphonium salts comprise also transformations offunctional groups in precursor salts. Thus, Hartley and coworkers obtaineda new cyclic nitrone spin trap, [4-(3’,3’-dibutyl-2’-oxy-3’H-isoindol-5’-yloxy)butyl]triphenylphosphonium bromide ((14), MitoSpin), bearing alipophilic cation which can easily permeate biological membranes due totheir hydrophobicity and large ionic radius while the large mitochondrialmembrane potential (150–170 mV, negative inside) causes the several-hundred fold accumulation of these cations in the mitochondrial matrix.The multi-step synthesis of (14) involves a novel Parham-type lithiation–cyclization, i.e., lithium–bromine exchange followed by intramolecular re-action between the resulting aryllithium and the isocyanate to give theisoindolinone core, oxidation of amine to nitrone, followed by phenolalkylation with 4-bromopropyltriphenylphosphonium bromide.10 Due tothe high propensity of MitoSpin to be oxidized, it has been suggested fortherapeutic use or as a probe to investigate mitochondrial oxidative stress invarious models. The hydrolysis in THF in the presence of HBF4 of 4-phosphoranylidene-5(4H)-oxazolones (15) yielded N-acyl-a-triphenypho-sphonioglycines (16) (R1

=H) while phosphonium salts (17), obtained byalkylation of (15), reacted with water in the absence of acidic catalyst toafford N-acyl-a-triphenylphosphonio-a-amino acids (16) (R1

=Me) or a-(N-acylamino)alkyltriphenylphosphonium salts ((18), R1

=alkyl, otherthan Me). Furthermore, salts (18) are also formed via decarboxylation of(16) on treatment with a Hunig base or on heating to 105–115 1C underreduced pressure.11

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NO

Ph3PO

R

NO

Ph3P

O

R

R1

R NH

OH

R1 PPh3O

O

R1 = H, Alk;

R NH

R1

PPh3OXH2O

HBF45 mm Hg,110-115 oC

iPr2NEt, r.t.

X=BF4, I

or

H2O

- CO2

X(15)

(16)

(17)

(18)

In the reaction of trihalophosphoranes with different anilines, thep-isomers of H2NC6H4R (R=p-Me, p–iPr, p-OMe, p-CO2Et) gave di(aryla-mino)phosphonium salts [Ph2P{NH(RC6H4)}2]Br as the sole reactionproducts, the corresponding o- and m-isomers leading to a mixture of similarsalts and aminophosphine oxides, while the disubstituted aniline 2,6-Me2C6H3NH2 gave the aminophosphine oxide Ph2(2,6-Me2C6H3NH)PO asthe only isolated product.12 Di(arylamino)phosphonium salts [Ph2P{NH(RC6H4)}2]Br obtained via the above mentioned direct aminolysis of diphe-nyltrihalophosphorane with p-substituted anilines provides a convenientaccess to a range of NPN ligands with various electron-withdrawing andelectron-releasing properties. In materials science, for the preparation ofpolyurethane foam-nanocomposites, diphosphonium montmorillonite (DP-MMT) was obtained by the intercalation of the quaternary diphosphoniumsalt [MeOOCCH2(Ph)2PCH2CH2P(Ph)2CH2COOMe]Br2.

13 In the context ofphosphonium salt syntheses and structures, one may note that analyzing theangle deformations at the phosphonium center in known tri(alkyl/phenyl)-(8-dimethylamino-naphth-1-yl) or tri(alkyl/phenyl)-(8-diphenylphosphinon-aphth-1-yl) phosphonium cations, Schiemenz concluded that they do notreflect hypercoordination byN/P or P/P bonding, but are largely the consequenceof steric crowding in the peri region.14 A review of stable noncyclic carbenesalso touches upon the subject of isolation and reactivity of phosphinopho-sphoniocarbenes and aminophosphoniocarbenes. The reactions of phosphino-carbenes provide an approach to scarce borylated and silylated stabilizedphosphorusylidesor theirmetal complexes (where themetal ise.g.,Al,Gaor In).15

The concept of ‘‘frustrated Lewis pairs’’ (FLPs) (sometimes also called‘‘antagonistic’’) inwhichLewis acid-base couples formedby sterically crowdedphosphines (or amines) and strongly electrophilic pentafluorophenylboranes isstericallyprecluded fromubiquitousneutralization reaction to form ‘‘classical’’Lewis acid/Lewis base adducts, is discussed in detail by Stephan and Erker inreviews.16,17 FLPs can exhibit rather special chemical relativities that resultfrom a probable cooperative interaction of the non-self-quenched pair andthe reviews cover aspects such as the use of FLPs in organometallic chemistry,H2 heterolytic splitting includingmechanistic studies of H2 activation by FLPsand applications in the metal-free catalytic hydrogenation of bulky imines,enamines, or enol ethers, aswell as activationofother smallmolecules byFLPs.The heterolytic splitting and activation of dihydrogen, stabilizing Hþ /H�

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pairs, for example in the form of the respective phosphonium cation/hydri-doborate anion salts of the type [R3PH

þ ][HBR13]� , is an important feature of

a variety of P/B or N/B pairs of this type, of which an increasing number ofexamples is presently emerging in the literature. The reversibility of H2 acti-vation for a few P/B pairs was examined with various experiments in orderto apply the reactivity of FLPs to develop new approaches to H2 storage.

18

The FLP derived from ClB(C6F5)2 and the bulky Lewis bases 2,2,6,6-tetra-methylpiperidine (TMP), tri-tert-butylphosphine, and tris(2,4,6-trimethyl-phenyl)phosphine was found to cleave H2 heterolytically to form theintermediate anion [HClB(C6F5)2]

� , which quickly underwent hydride/chloride exchangewith the remainingClB(C6F5)2 togive theknowncompound[HB(C6F5)2]n (n=1 or 2) with the anion [Cl2B(C6F5)2]

� presenting in thecorrespondingproducts suchas the salts [TMPH][Cl2B(C6F5)2], [

tBu3PH][Cl2B(C6F5)2], and [Mes3PH][Cl2B(C6F5)2], respectively. Furthermore, the Lewisadduct t-Bu3P-BH(C6F5)2 was found capable of generating a FLP at elevatedtemperature, the reaction of which with H2 produced the splitting product[tBu3PH][H2B(C6F5)2].At the same time,Mes3P did not form theLewis adductwith [HB(C6F5)2]n, but gave the FLP, which was also capable of splittingH2 toyield initially [Mes3PH][H2B(C6F5)2] (followed by disproportionationto form [Mes3PH][HB(C6F5)3],Mes3P, [H2B(C6F5)]2, andH2). Similarly, 2,4,6-tri-tert-butylpyridine (TTBP) and [HB(C6F5)2]n gave in the presence of H2

the final products [TTBPH][HB(C6F5)3] and [H2B(C6F5)]2. The contrastingreactivities of the tBu3P/[BH(C6F5)2]n and Mes3P/[HB(C6F5)2]n pairs wereexplained on the basis of the different pKa values of the [LBH]þ cations.19 Incontinuation, para-substitution found previously for classical phosphineadducts of B(C6F5)3 under warming to yield the air- and moisture-stablezwitterions R3P-C6H4B(F)(C6F5)2, was observed for smaller phosphines afterthe combined toluene solutions of the reagents were heated under reflux,confirming the general character of this reaction.20

In computational studies of H2 activation by FLPs, Papai and co-workerssuggested generation of a phosphine-borane ‘‘encounter complex’’, stabil-ized by H���F interactions. In this ‘‘species’’ the boron and phosphoruscenters approach but fail to form a dative bond as a result of steric con-gestion. Interaction of H2 in the reactive pocket between the donor andacceptor sites results in heterolytic cleavage of H2.

21 A related mechanismhas been described for phosphine-boranes R2PC6F4B(C6F5)2 in the othermechanistic studies.22 However, the subsequent computational studies byGrimme et al.23 raised some doubt on the ‘‘reality’’ of the suggested(quasi)linear P���H-H���B activation transition state as the quantumchemical method (B3LYP) used is well-known to overestimate steric con-gestion. With properly dispersion-corrected density functionals, no lineartransition state exists and only one minimum with a rather large H–Hdistance of about 1.67 A could be found. This points to an alternativebimolecular mechanism in which the ‘‘entrance’’ of H2 into the ‘‘frustrated’’P���B bond is rate-determining. Additionally, Rajeev and Sunoj usingab initio and DFT methods investigated the factors responsible for thereversible hydrogen-activation ability on the model of (CH3)2P-C6F4-B(CF3)2) and estimated the energies of various intermediates, generated bythe addition of molecular hydrogen, and their interconversion barriers.24

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The reactions of FLPs with alkenes, aldehydes, and a variety of othersmall molecules, including carbon dioxide, in cooperative three-componentprocesses, offer new strategies and perspectives for synthetic chemistry.Thus, the FLP formed by the combination of tBu3P and B(C6F5)3 reactswith 1,3-dienes to give zwitterionic 1,4-addition phosphonium borates, e.g.,(19), the geometry of which appears to be dominated by the steric demandsof the substrate.25 Estimation of the ability of phosphonium borates of theform [R3PH][B(C6F5)4], R2PHC6F4BF(C6F5)2 and R2PHC4H8OB(C6F5)3(R2=Cg2, Mes2, tBu(Mes), tBu2) as well as the phosphine-boranesR2PC6F4B(C6F5)2 to activate CpTiMe2(NPtBu3) for olefin polymerizationboth in stoichiometric and catalytic reactions, suggest that metal-basedFLPs are uniquely reactive.26 Indeed, these activators give highly activecatalysts despite the liberation or initial provision of a free phosphine. Thephosphonium borate activators function via protonation of a metal–alkylbond while the latter abstract methyl to form a methyl-borate anion.

Frustrated Lewis pairs may also add to alkynes. In this way, the FLPgenerated from B(C6F5)3 or (PhMe)Al(C6F5)3 and (o-C6H4Me)3P reactswith PhC�CH to give the zwitterionic species (20). However, sometimes(sp)C-H deprotonation competes with formation of the addition productand the FLP derived from tBu3P gave, in a similar reaction, the salts (21) innear quantitative yields. The isolated and classical Lewis acid/base adductPh3PB-(C6F5)3 was also shown to react with PhC�CH to give the additionproduct, Ph3PC(Ph)=C(H)B(C6F5)3. This result is surprising in that for theadduct Ph3PB(C6F5)3 no evidence of dissociation was found by NMRspectroscopy.27 These data allowed Stephan to suggest that the accessibilityof frustrated Lewis pair chemistry from classical Lewis acid/base adductsoffers the possibility that many more examples of compounds, otherwisethought to be unreactive, may indeed offer access to new reactivity. In thestudy of the reactivity of the intramolecular FLP (22), generated in situ bytreatment of Mes2P-CH=CH2 with 1 equiv of HB(C6F5), Erker and cow-orkers demonstrated that only the C-H cleavage pathway was observed inthe reaction with 1-pentyne to yield salt (23).The reaction between (22)and trans-cinnamic aldehyde resulted in the zwitterionic six-membered1,2-addition product to the carbonyl group (24). FLP (22) regioselectivelyadded to the electron-rich C=C double bond of ethyl vinyl ether andunderwent an exo-cis-2,3-addition to norbornene to afford zwitterionic

(o-Tol)3P H

E(C6F5)Ph

E = B, Al

Ph E(C6F5)3

[tBu3PH]Mes2P B(C6F5)2

(22)

Mes2PB(C6F5)2

H

Mes =

Mes2PO

B(C6F5)2

H

Ph

Mes2P B(C6F5)2

HO

BMes2P

(C6F5)2

tBu3P

B(C6F5)3

Me

Me

(19) (20) (21)

(23) (24) (25) (26)

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species (25) and (26), respectively, by B-O and P-C bond formation. Acombined experimental/theoretical study suggests that this reaction takesplace in an asynchronous concerted fashion with the B-C bond beingformed in slight preference to the P-C bond.28

Employing strategies based on frustrated Lewis pair chemistry, newroutes to phosphino-phosphonium cations and zwitterions have beendeveloped. Thus, the reaction of B(C6F5)3 with H2 and diphosphine tBu2P-PtBu2 was accompanied by heterolytic hydrogen activation and yieldedthe phosphino-phosphonium borate salt [(tBu2P)P(H)tBu2][HB(C6F5)3].Alternatively, alkenylphosphino-phosphonium borate zwitterions (27)-(29)were obtained from the reaction of B(C6F5)3, phenylacetylene and P2Ph4,P4Cy4, or P5Ph5. One of the P centers of the di(poly)phosphine adds to thephenyl-sustituted carbon atom of the alkyne, while the borane has addedto the unsubstituted end of the alkyne, affording a trans-orientation of theB and P about the resulting olefinic C=C bond. A related phosphino-phosphonium compound (30) was also isolated from the thermolysis ofB(C6F5)3 and P5Ph5 mixture.29

Ph B(C6F5)3

HPh2P

PPh2

Ph B(C6F5)3

HPCy

PCy

CyP

CyP

Ph B(C6F5)3

HPPhPhP

PhPPPh

PPh

P

PhPPhP

PhP PPh

B(C6F5)2

FFF

F F

Ph

(27) )92()82( (30)

Completing this topic, the phosphonium boranes of general formula[p-(Mes2B)C6H4(PPh2R)]þHlg� (R=Me, Et, n-Pr), Ph, in which Lewisacidity increases with their hydrophobicity, react reversibly with water toform the corresponding zwitterionic hydroxide complexes of generalformula p-(Mes2(HO)B)C6H4(PPh2R) and react with fluoride ions to formthe corresponding zwitterionic fluoride complexes of general formulap-(Mes2(F)B)C6H4(PPh2R). Among compounds tested, the tetraphenyl-phosphonium derivative (R=Ph) has been revealed as a promisingchemosensor-candidate for drinking water analysis for fluoride ions.30

2.2 Applications in synthesis

Phosphonium salts are known as useful reagents, catalysts and intermedi-ates in general organic synthesis. In this context, a review of the mostrecently-developed coupling reagents used for amide bond formation,discussing pros and cons for each case, should be mentioned as a fewfamilies of coupling reagents, e.g., those based on 1H-benzotriazoles(HOBT), pentafluorophenol (HOPfp), 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine (HODhbt) or those of the halo-phosphonium type, involvinga phosphonium group.31 Note that the advantage of phosphonium saltssuch as BOP (31) as coupling reagents consists in not yielding guanidiniumby-products via reaction of the coupling reagent with amines. For example,the BOP-catalysed coupling of the monobenzyl ester of the N-Cbz-protected phosphonate derivative of norleucine with the hydroxyl moietiesof derivatised L-lactic or glycolic acid was especially advantageous for

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the efficient solution synthesis of norleucine-derived phosphonopeptidesmimicking the peptide sequences Nle-Gly(Ala) and Nle-Gly(Ala)-Val.32

However, the phosphonium coupling reagents may also have other appli-cations. Recently, the phosphonium coupling of unactivated and unprotectedtautomerizable heterocycles which proceeds via the C–OH bond activationof a heterocycle with a phosphonium salt (e.g., BOP) and subsequentfunctionalization with nucleophile, has emerged as a new, mild, efficient,chemoselective and versatile methodology for direct C–C, C–N, C–O, andC–S bond formation. This powerful and protecting-group-free practicalmethodology is applicable to many biologically important heterocyclesincluding macromolecules with sensitive functionalities (e.g., DNA, RNAand PNA building blocks), allowing a domino multiple-step process in asingle step, has also been highlighted in a detailed review. 33 A new exampleof a similar reaction describes the application of 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) in thepresence of DBU for the conversion of tert-butyldimethylsilyl (TBDMS)-protected guanosine and 2’-deoxyguanosine to the corresponding stableand storable O6-(benzotriazol-1-yl) derivatives, which under the action ofnucleophiles, provided the C-6 modified 2-amino purine nucleosideanalogues.34 The mechanism of production of O6-(benzotriazol-1-yl)derivatives, elucidated using the 31P NMR technique, involves formation ofthe intermediate nucleoside phosphonium salt (32). The other syntheticapproach to N6,N6-dialkyladenine nucleosides is based on the application,instead of BOP, of the combination PPh3/I2/HOBt or that using hexaalk-ylphosphorus triamides generated in situ, which is advantageous in terms ofhigher yields and product purity. In this case the reaction apparentlyproceeds via the formation of phosphonium salts, [(Ph3P

þ I)I–] or[(Et2N)3P

þ I)I–], which react at the amide carbonyl group of the hypox-anthine residue to afford a nucleoside phosphonium salt followed bysubstitution by a nucleophile.35 Application of excess of triphenylphosphinedibromide [Ph3P

þBr]Br� in the presence of a base also provided aconvenient protocol for the conversion of carboxylic acids to their esters inmoderate-to-high yields (30–95%). For chiral acids, the reaction proceededwith little or no racemization. Use of a chiral alcohol in this transformationgave the ester with retention of configuration at the stereogenic center. Themethod relies on the in situ conversion of triphenylphosphine dibromide toan alkoxyphosphorane, which serves as the virtual esterification agent.36

A general and flexible approach to highly substituted 1,3-dienes and 1,3,5-trienes has been developed via the reaction of an allylic alcohol withPPh3 �HBr in methanol, followed by treatment of the intermediate phos-phonium salt (33) with aldehydes in the presence of a base.37 The easilyprepared, air-stable phosphonium salt (34) was used as a key substratein the facile synthesis of the chiral iron complex trans-(R,R)-[Fe(NCMe)2(PPh2CH2CHNCHPhCHPh-NCHCH2PPh2)](BPh4)2, the P-N-N-P tetra-dentate ligand being an efficient catalyst for the asymmetric transferhydrogenation of ketones.38

Transformation to phosphonium salts was used in a convenientprocedure for the separation of sym and asym-isomers of phobane(s-PhobPH and a-PhobPH, respectively). The investigation was prompted by

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the extensive use of alkylphobane complexes in catalysis where, however, themixtures of phobane isomers often employed complicates the discussion andinterpretation of the catalytic results in terms of ligand stereoelectronics. Thesuggested methods for separation are based on the different reactivity ofphobane isomers. Thus, the more basic s-PhobPH undergoes selective proto-nation with HCl in ether, while a-PhobPH can be selectively oxidized. Com-bination of these procedures allowed, after neutralization followed by hexaneextraction, the isolation of s-PhobPH in 92% yield, the hydrophilic a-Phob-P(O)H remaining in the aqueous phase. Alternatively, among the hydro-xymethyl phosphonium salts s-(35) and a-(35) obtained as amixture of isomersvia reaction of phobanewith aqueous formaldehyde in the presence ofHCl, theasymmetric isomer a-(35) readily undergoes selective deformylation aftertreatmentwith 0.5 equiv ofNaOHto give a-PhobPCH2OH in a toluene extractwhile theother isomeric salt s-(35) remains in the aqueousphase.39The reactionof substituted (2-aminobenzyl)triphenylphosphonium bromides (36) witharomatic aldehydesora,b-unsaturatedaldehydes constitutes anew synthesisof2,3-disubstitued indoles. Themethod combines a two-step approach involvingimine formation and six-electron ring closure, followedbya 1,5-hydrogen shift,in an efficient, rapid one-pot procedure.40 Mazurkiewicz et al. suggested usingthe above-mentioned 1-(N-acylamino)alkyltriphenylphosphonium salts (18)as synthetic equivalents of N-acylimines and new effective a-amidoalkylatingagents.41The idea is based on the transformation of the above salts to enamidesRC(O)-NH-HC=C(H) which proceeds directly under the action of Hunig’sbase or as a result of slow tautomerization of 1-(N-acylaminoalkyl)amidiniumsalts formed in the reaction of phosphonium salts with DBU in MeCN.Therefore, (N-acylamino)alkylphosphonium salts (18) as well as amidiniumsalts or enamides derived from them, react with dialkyl malonates in thepresence of DBU to give the corresponding amidoalkylation products.

P

NPh

MePh

O

O

Me

MeX

NN

N

O P(NMe2)3PF6

BOP

N

NN

N

OP(NMe2)3

NH2O

RO

OR X

X = H, OTBDMS

PPh3Br

PF6

PPh3Br

Ph

NH2R

R = H, o-, m-, p-Cl, Br, F, OMe

PP

HOH2C CH2OHHOH2C CH2OH

s-(35) a-(35)

Ph2P

PPh2

OH

HO

2Br

(31) )43()33()23(

(36) (37)X = Cl, OTf

F. Mathey et al. reported that 7-R-7-phosphanorbornenes (37) can beconsidered as synthetic equivalents of nucleophilic phosphinidenes [RP] onthe basis of their transformation into phosphinites by quaternization and

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alcoholysis via the sequence [R–P]þR1X - RR1PXþ R2OH - RR1P–OR2, in the presence of triethylamine.42 Later on they demonstrated that thehydrolysis of the phosphanorbornenium triflate ((37), X=OTf) can bedirected by manipulating the pH of the reaction medium. Thus, the salt doesnot react with neutral water but is rapidly hydrolyzed in the presenceof triethylamine to give the expected bicyclic tertiary phosphine oxide(as a mixture of two isomers) due to the cleavage of one P-C bond of thephosphonium bridge, while in the presence of a-picoline the hydrolysisafforded methylphenylphosphinous acid Me(Ph)P(O)H as the sole product.According to DFT calculations, the basicity of a medium determines thehalf-life of the intermediate hydroxyphosphorane, which is sufficiently longin weakly basic media, allowing the total loss of the bridge to give thephosphinous acid while fast deprotonation in strongly basic media inducesthe collapse toward the tertiary phosphine oxide.43

Recently, the number of reports of phosphines acting as nucleophiliccatalysts has increased significantly. The reactions are proposed to startfrom the nucleophilic addition of phosphines to generate reactive zwitter-ionic intermediates, i.e., phosphonium salts. In rare cases such intermediatesalts were either isolated or their structures were established on the basis ofNMR data but mostly their formation was proposed from a generalchemistry point of view. Among publications in the field of phosphinecatalysis, in this chapter we will mention those which discuss the formationof intermediate phosphonium salts and their structure. In this context, areview of the Rauhut–Currier reaction, being the phosphine-catalyzeddimerization of electron-deficient alkenes, acrylonitrile and ethyl acrylate,should be also mentioned.44 The transformation is believed to proceed viareversible conjugate addition of a nucleophilic catalyst, i.e. trialkylpho-sphine or triarylphosphine, to an alkene, giving a zwitterionic species,followed by the Michael addition of the second equivalent of activatedalkene and subsequent prototropic shift and extrusion of the phosphinecatalyst to generate the coupling product. The review covers both historyand synthetic applications, including both inter- and intra-molecularreactions and their asymmetric versions as well as tandem processesand applications in total synthesis. Furthermore, a triphenylphosphine-catalyzed [3þ 3] annulation reaction of modified tert-butyl allylic carbon-ates with various alkylidenemalononitriles performed in protic solventresults in substituted cyclohexenes, while using non-polar solvent such astoluene or xylene afforded only non-cyclized products.45 Similarly, a tri-phenylphosphine-catalyzed (10 mol%, toluene, reflux) [4þ 3] annulationof modified allylic carbonates with methyl coumalate yielded thebicyclo[3.2.2]nonadiene skeleton with high stereoselectivity.46 Reporting aphosphine-catalyzed [Ph3P or (4-FC6H4)3P] [3þ 2] annulation of g-methylallenoates with aromatic aldehydes, readily affording 2-alkylidenetetrahy-drofurans, the authors discuss the possible reaction scheme in which thephosphorus ylide (39), generated from the phosphonium dienolate (38) byan overall 1,4-hydrogen shift, is believed to be the key intermediateresponsible for the [3þ 2] annulation and other transformations of g-methylallenoates with aldehydes.47

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R' PR3

COOEt

R' PR3

COOEt

R'

PR3

COOEt

1,4-H-shift

R'

PR3

COOEt

(38a) (38b)

(39a) (39b)

Cl

Cl

CN

CN

OH

OPPh3

HNP

O

ArNMe2

BrBr

PhNR

(40)(41)

Selective N-monoalkylation of aromatic amines with primary andsecondary alcohols as well as conversion of aromatic amines to amides canbe performed in excellent yields using triphenylphosphine (PPh3) and 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as a promoting system indichloromethane at room temperature. This reagent system also allowedperforming the symmetrical and unsymmetrical N,N-dialkylation of aro-matic amines. The suggested mechanism to explain this transformationinvolves the initial formation of the known quaternary phosphonium saltthrough the addition of DDQ to Ph3P in which the negatively chargedoxygen in the hydroquinone part of the adduct can act as a base todeprotonate the amine to give salt (40), and hence no additional base isrequired for generation of an amine anion.48 The intermediate formation ofthe phosphonium salt (41) was also postulated for the synthesis of substi-tuted quinolines from a-arylamino ketones in the presence of the Vilsmeierreagent PBr3/DMF.49

Tributylphosphine induces a reaction between methyl 4-hydroxybuty-noate and N-tosylimines to afford 4-methylene-1,3-oxazolidines. Interest-ingly, phosphines such as PPh3 or P(iBu)3 were found to be inactive,probably due to their lower nucleophilic character compared to PBu3. Sincethe postulated role of the phosphine is primarily to generate a strong base,the authors estimated and succeeded in performing this cyclization in thepresence of other organic or inorganic bases, namely DMAP and K2CO3.

50

An elegant approach to acene dinitriles and diesters was developed on thebasis of the reaction of aromatic ortho-dialdehydes and trialkylphosphinesin combination with diethyl maleate or fumaryl nitrile in the presence ofDBU. The reaction combines in situ generation of a phosphorus ylide via aphosphonium salt followed by the Wittig olefination and subsequentintramolecular Knoevenagel condensation. The acene diesters thus pro-duced can be converted into dialdehydes and undergo a further round ofiterative reactions, hence providing the homoelongation protocol.51 Thiscascade reaction was also used for the synthesis of benzo[c] and naphtho[-c]heterocycle diesters and dinitriles.52 The other example comprised thethree-component synthesis of trisubstituted alkenes with excellent stereo-selectivity from readily-available aldehydes, a-haloacetates, and terminalalkenes in the presence of phosphine and without requiring bases. In generalthe reaction may be considered as a one-pot tandem Wittig reaction. Thesuggested reaction mechanism comprises Michael-type addition of phos-phine to an electron-deficient alkene to generate the corresponding

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zwitterion which might serve as an organic base to deprotonate the otherphosphonium salt, formed by the nucleophilic attack of the phosphine onthe a-halocarbonyl compound. The resulting phosphorus ylide reacts withaldehyde to afford the final product.53 Furthermore, triphenylphosphinein combination with N-bromosuccinimide was used for the activation ofthe carboxylic acid and alcohol in the synthesis of thioesters, in whichtetrathiomolybdate was the sulfur source. The authors suggested theintermediate formation of two phosphonium salts, one based on a carb-oxylic acid, i.e., RC(O)OPþPh3Br

� , and the second, ROPþPh3Br� ,

derived from the alcohol.54

Werner has reviewed the data up to 2008 concerning the applications ofphosphonium salts as Lewis acid catalysts for a variety of C-C, C-O and C-N bond forming reactions as well as the use of chiral P-salts as asymmetricphase-transfer catalysts.55 New examples dealing with direct application ofphosphonium salts in asymmetric organocatalysis should be also men-tioned. T. Ooi and co-workers56 described a practical method for the in-corporation of a wide variety of chiral, non-racemic quaternary a-aminoacids at specific sites of a peptide strand. The method involves the direct andhighly stereoselective construction of quaternary stereogenic carbon centerson C-terminal azlactones of growing peptides by alkylation under organic–aqueous biphasic conditions in the presence of a catalytic amount of anoptically pure, D2-symmetric tetraaminophosphonium salt (42) as a chiralphase-transfer catalyst. The alkylated azlactone can be further employeddirectly for peptide ligation, and appropriate repetition of the alkylation–ligation processes provides a practical strategy for the synthesis ofoligopeptides with incorporation of quaternary a-amino acid residues of thedesired configuration into a specific site of the peptide strand. The sameresearch group successfully applied the R,S-tetra(binaphthylamino)pho-sphonium salt (43) as a charged Brønsted acid in catalytic enantioselectiveconjugate addition of arylamines to nitroolefins.57 A homochiral arylami-nophosphonium cation with a [7.7]-spirocyclic core was initially prepared asa chloride salt but the chloride anion had to be exchanged for barfate[(3,5-(CF3)2-C6H3)4B

� (BArF)] for successive catalysis. Interestingly, theR,R-isomer of this salt catalyzed the above transformation but provided lowenantioselectivity. Furthermore, the generation of a reactive chiral tetra-aminophosphonium phosphite, the formation of which has been detectedby low-temperature NMR, from the salt (44) under the action of KOtBuand dialkyl phosphites, allowed the ready (at –98 oC in THF solution)enantioselective hydrophosphonylation of aromatic aldehydes (ee 91-98%).58 The other binaphthyl chiral phosphonium salt (S)-(45), used in 1mol% amount, promoted efficient, enantioselective Michael addition of 3-aryloxindoles to methyl(ethyl) vinyl ketone and acrolein with exceptionallyhigh enantioselectivity under phase-transfer conditions and was effectivein the asymmetric Mannich reaction of 3-aryloxindoles and activatedimines with excellent diastereoselectivity and high enantioselectivity.59

Importantly, the optically active Michael adducts derived from 3-arylox-indoles can be readily transformed into valuable natural products andtheir analogues.

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Ar=H,Ph 3,4,5-F3-C6H2

PBu

Bu

Ar

Ar

NP

N

N

N

BrAr Ar

ArAr

Ph

Ph

Ph

Ph

Ar = Ph, 3,5-(Me3Si)2-C6H3, 3,5-(tBuMe2Si)2-C6H3

N

NH

P

Ar

Ar

(S)-

N

N

H H

H H

(R)-

Cl

BArF = [3,5-(CF3)2-C6H3]4B

NH

P

HN

NH

HN

Cl

ArAr Ar

Ar

H

H

Ar = Ph, 4-CF3-C6H4, 4-Me-C6H4, 4-MeOC6H4

BArF

(42) (43) (44) S-(45)

Ar= 3,5-(CF3)2-C6H3

2.3 Application as ionic liquids

This active research area is focused both on application of phosphoniumILs as efficient reaction-promoting media in synthetic procedures as well assynthesis of novel ILs and their applications for other purposes. The recentdevelopments in the field of ionic liquids (ILs), including the phosphoniumones, from their fundamental properties to the applications in catalyticprocesses and use for biomass treatment have been highlighted in a detailedreview.60 Phosphonium salts as ionic liquids are known to have some ad-vantages over imidazolium and pyridinium ILs such as higher thermalstability, faster kinetics of the salt formation, absence of an acidic proton(which makes them stable towards nucleophilic and basic conditions), beingof lower density than water (which provides potential benefits for someapplications) and are reasonably cheaper on an industrial scale. Prepar-ations of phosphonium ILs and their applications in general organicsynthesis including Diels-Alder, Heck, Suzuki, Buchwald-Hartwig, Friedel-Crafts, Kornblum substitution, Grignard, carbonylation, transfer hydro-genation, hydroformylation, esterification reactions, etc. (the literature since2000) are the main topics of a special review.61 However, in contrastto imidazolium ILs, phosphonium ILs are rarely used as a medium for thehalogenation of organic compounds, as is obvious from yet anotherreview.62 This gap was filled with tridecylmethylphosphonium/trihexylte-tradecylphosphonium trihalides (Br3

� , BrCl2� or ClBr2

� ) designed aseffective halogenating agents.63 Methylation of tertiary amines or phos-phines with dimethyl carbonate presents a procedure for the synthesis ofhalogen-free methyl-onium (methylammonium and methylphosphonium)methyl carbonate ionic liquids which, after anion-exchange, afford a rangeof derivatives with different melting points, solubility, acid–base properties,stability and viscosity.64 Furthermore, treatment of methyl carbonate saltswith water yields strongly basic bicarbonate ILs, which efficiently catalyzethe Michael additions. This work also suggested NMR spectroscopy of theneat ionic liquids as a probe for solute–solvent interactions as well as atool for characterization. Some other new phosphonium salts that weresuggested as ILs this year, include phosphonium perchlorates obtained frominexpensive ammonium perchlorate as a perchlorate source,65 and (3-ami-nopropyl)tributylphosphonium aminoacid salts were obtained by neutral-ization of the corresponding phosphonium hydroxide with 20 natural aminoacids. The aminoacid salts were found to be useful for CO2 capture (up to

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1 mol CO2 per mol of ionic liquid, i.e., twice than reported before).66 Linderand Sundermeyer described the three new fluorinated anions (C6F5)2N

�

[BPFPA], C6F5(CF3SO2)N� [PFTFSI], and C6F5(C4F9SO2)N

� [PFNFSI]to impart highly hydrophobic properties, water immiscibility and hydrolyticstability for both imidazolium and phosphonium ionic liquids.67 For the syn-thesis of ILs bearing these anions, deprotonation of 1,2-dimethyl-3-alkylimi-dazolium salts (alkyl=ethyl, n-butyl, n-octyl) or tributylmethylphosphoniumsalts, respectively, by strong bases such as NaNH2, KH or KOtBu followed byreaction of the purified 1-methyl-2-methylidene-3-alkylimidazolines or thecorresponding Bu3P=CH2 ylide with the corresponding fluorinated acids wasused. Other new imidazolium andphosphonium ILs containing anions derivedfrom superacids, in particular 1,1,2,2-tetrafluoroethanesulfonic acid (TFESA)and 1,1,2,3,3,3-hexafluoropropanesulfonic acid (HFPSA), were suggested asreaction media for improved chemical processing for some industriallyimportant chemical reactions (alkylation, etherification and isomerization).Using such ILs, the reactionmixturesmostly present as a single phase, allowinghigh reaction rate, and separate into two phases upon completion of thereaction.68 The above ILs are obtained via the reaction of parent ILs withchloride anion with potassium salts of superacids in acetone.

Tindale and Ragogna69 reported the synthesis of another class of highlyfluorinated phosphonium ionic liquids (HFPILs) (46) that are thermally stableand liquid at room temperature. The synthetic procedure involvedthe synthesis of a fluorinated alkyl phosphine, RP[(CH2)2Rf8]2 (R=2,4,4-trimethylpentyl; Rf8=(CF2)7CF3), by the radical addition of RPH2 to afluorous olefin, followed by the quaternization of the fluorinated phosphinewith a fluorous iodide, I(CH2)2Rf2, and subsequent anion exchange. Tointroduce a thiol functionality to the cation, fluorinated phosphine,P[(CH2)2Rf6]3, was reactedwith a 1-bromododecylthiol.Deposited films of theHFPIL materials on Ag coated Cu substrates are capable of producing watercontact angles greater than 160o, indicating that HFPILs are suitable assuperhydrophobic coatings, the additional functionality in the cation pro-vidingfilmswith increaseddurability.Vice versa, cationic exchange allowed thepreparation of intrinsically photochromic ionic liquids by simple combinationof sodium methyl orange, a well-known example of a photochromic azo-benzene derivative, and the appropriate phosphonium cations. These novelsalts (47) are light responsive and maintain the properties of ionic liquids.70

Trihexyltetradecylphosphonium based ILs with dodecylbenzene-sulfonateand bis(2,4,4-trimethylpentyl)-phosphinate anions were found to be suitablemedia both for extraction of lactic acid (LA) from the fermentation broth andfor the further enzymatic synthesis of ethyl lactate via esterification of LAwithethanol. Further improvement of the esterification reaction is possible usingmicrowave irradiation, which enhanced ethyl lactate production, acceleratingthe hydrolysis of lactoyllactic acid (the linear dimer of LA) and providingmorelactic acid as substrate.71 Solubility of the carbohydrates (glucose, fructose,sucrose, and lactose) was estimated for twenty eight different ILs includingthose with a tetraalkylphosphonium cation.72 Hydrophobic ILs were found toextract a large quantity of glucose from an aqueous solution and some

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selectivity in the partition studies was observed, e.g., trihexyl(tetradecyl)pho-sphonium chloride ([C14H29(C6H13)3P]Cl) can extract a large quantity of di-saccharide mixtures, but is not so efficient at extracting monosaccharidemixtures. Furthermore, Guibal et al., focusing on novel extractant-impreg-nated resins (EIR) combining the potential of extractants (liquid/liquid ex-traction) and resin (sorption processes) for metal recovery, developed a newclass of EIR by IL-immobilization in biopolymer matrices with a special at-tention to [C14H29(C6H13)3P]Cl /alginate with application to the sorption ofmetals suchasPd(II), Pt(IV),Au(III),Hg(II), andBi(III).73Trihexyltetradecyl-phosphonium tetrafluoroborate was also suggested as a suitable mediumfor the mild oxidation of aryl halides to corresponding aldehydes usingiodoxybenzoic acid as an oxidizing agent.74

The photo-, thermo- and solvatochromic properties of 2,3-dihydro-1’,3’,3’-trimethyl-6-nitrospiro[1-benzopyran-2,2’-1H-indole] (BSP) and its photo-induced merocyanine isomer (MC) were investigated in phosphonium basedILs by UV-vis absorption spectroscopy and the kinetics and thermodynamicsof the BSP3MC equilibrium were found to be sensitive to the nature ofthe anion.75 For example, the MC lmax shifted from 560 nm to 578 nm insolutions of [Me(C4H9)3P][tos] and [C14H29(C6H13)3P][dca], respectively. TheBSP isomer was highly favoured at equilibrium in the ILs studied.

N

S

N

N

O

O

O[(C6H13)3(C14H29)P]

P R

Rf6

Rf8

Rf8 A

Rfn = (CF2)n-1CF3

A = I, PF6, BF4, NTf2, OTf, OTs

A = Br, NTf2

R=C14H29, CH2OC3H7, CH2OC5H11, CH2OC3H7, CH2OC8H17;A= (CN)2N, (CF3SO2)2N, BF4, NO3, CH3OSO3

C6H13 P

C6H13

R

C6H13

A

SN

O

O O

[Sac]O S

N

O

OO

[Acc],

(46) (47) (48)

R = CH2CH(CH3)CH2C(CH3)3

R= CH2(CH2)10CH2SH

In contrast to typical organic solvents, rhodium-catalyzed transfer hydro-genation of the C=C bond of chalcone and some other a,b-unsaturatedketones proceeds chemoselectively in a range of ionic liquids, including thephosphonium-based ones. This phenomenon suggests that there is an inter-action between the carbonyl group of the substrate and the ionic liquid whichprevents reduction of the carbonyl group.76 The use of ionic liquids for theimmobilization of rhodium siloxide complexes has permitted development ofbiphasic systems which, when applied as catalysts for hydrosilylation offunctionalised olefins, combine the advantages of homogeneous catalysts (highcatalytic activity) and heterogeneous ones (easy separation and possibilityof recycling). Among the range of phosphonium ionic liquids (48) tested in thisstudy, the rhodium siloxide complex [{Rh(m-OSiMe3)(cod)}2] immobilisedin propoxymethyltrihexylphosphonium saccharinate IL (R=CH2OC3H7,A= Sac) was the most efficient system.77

In general, ILs are suggested as ‘‘greener’’ alternatives to commonorganic solvents, since they usually display no measurable vapour pressure

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and are non-flammable, therefore eliminating the safety and environmentalproblems often associated with volatile organic solvents. However, phos-phonium ILs, including those in which one of the alkyl substituentscontained ester, ether, alcohol or alkene functionality in order to promotebiodegradation, showed relatively low levels of biodegradability (r30%,the mark required for classification as ‘readily biodegradable’ is W60%) inthe CO2 headspace test (ISO 14593).78,79 These data should be taken intoaccount as the release of non-biodegradable organic substances into theenvironment, even when non-toxic, can lead to bioaccumulation, which inturn might result in chronic toxic effect.

Finally, taking into account the growing general interest in ILs, thesecompounds have also become the subject of computational studies, e.g.,molecular dynamics simulations were performed for one of the phos-phonium-based ILs, namely trihexyl(tetradecyl)phosphonium bis(trifluoro-methylsulphonyl)imide.80

2.4 Coordination properties

Phosphonium salts are of interest for construction of differentmetal complexes.The stepwise deprotonation of [Ph2P{NH(C6H4i-Pr-p)}2]Br, followed by thereaction of the intermediate lithium aminoiminophosphoranate [(NPN)Li]with palladium and platinum precursors in different ratio, provided newk2-aminoiminophosphoranate palladium and platinum complexes, i.e.(NPN)Pd(PPh3)Cl, (NPN)2Pd, (NPN)Pt(Z2-C2H4)Cl, and (NPN)Pt(PPh3)Cl.

81

In the reaction of the Roper’s complex [Ru(CO)2(PPh3)3] with[HC�CCH2PPh3]Br, the product obtained was described as a complex of aphosphonioallene [Ru(Z2-H2C=C=CHPPh3)(CO)2(PPh3)2]Br (on the basis ofcrystallographic data for its metathesis product [Ru(Z2-H2C=C=CHPPh3)(CO)2(PPh3)2]2Br(PF6) and a comparison of spectroscopic data with those forthe simple allene analogue [Ru(Z2-H2C=C=CH2)(CO)2(PPh3)2]).

82 Reactionof [Ru(CO)2(PPh3)3] with phosphonium salt [Me3SiC�CPPh3]OTf in thepresence of moist [nBu4N]F proceeds as fluoride-mediated desilylation yieldingthe C-H activation product [RuH(C�CPþPh3)(CO)2(PPh3)2]OTf.83 Based oncomputation and IR spectroscopy data, the authors suggest that the startingalkynyl salt is a poor acceptor ligand, weaker than conventional isonitriles. Fivemembered osmacycle (49) bearing the phosphonium moiety, can be readilyprepared from the reaction of OsCl2(PPh3)3 with HC�CCOOEt. Reactionsbetween osmafuran (49) and alkynes (HC�CHPh or HC�CCH(OH)Ph)proceeded via insertion of the latter (ring-expansion reactions) providing easyapproach to nine-membered osmacycles, such as e.g., (50) or (51), under mildconditions and in good yield.84

(49)

OsO

PPh3

Cl

OEt

PPh3

Cl

Ph3POs

OPPh3

OEt

PPh3

Cl

Ph3P

HHH

O

Ph H

ClOsO

PMe3

OEt

PPh3

Cl

ClPh

H

Ph H H

(50) (51)

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The reactions of tetraphenylphosphonium azide and chloride or theirtriphenylsulfonium analogues with silver azide furnished the correspondingonium salts [Ph4P][Ag(N3)2] and [Ph3S][Ag(N3)2], respectively, bearing thenovel diazidoargentate anion, the structure of which was elucidated byX-ray crystallography.85 Application of phosphonium cations such asmethyl- or ethyl-triphenylphosphonium, benzyltriphenylphosphonium, andethane-1,2-bis(ethyldiphenylphosphonium), as counterions, allowed isol-ation and structural characterization of remarkably stable crystalline saltscontaining the m-oxido-bis{cis-tetrachloridooxidorhenate(VI)} anion.These salts are of special interest as Re(VI) is uncommon and regarded asunstable with the exception of rhenium(VI) oxide and its melts. The syn-thetic approach was based on the reaction of the corresponding Re(VII)phosphonium salts with gaseous HCl and again with Re(VII) anion.86

Interestingly, although the tetrahedral environment of P atoms as well asthe usual propeller-like symmetry of the -PPh3 moiety are essentially con-served in Re(VI) salts, the conformations are not strictly the same as in theiranalogues with Re(VII)-containing anions. Starting from K2PtCl4 orK[PtCl3(C2H4)]3H2O (Zeise’s salt) and tetrabutylphosphonium bromide,several Pt(II)-bromido complexes with the (nBu4P)

þ counter cation wereobtained in good to high yields. This study has also served to clarify a fewimportant points in the ethylene hydroamination process catalyzed by thePtBr2/nBu4PBr system.87

Phosphonium salts are also able to form host-guest complexes. An elec-trospray ionization mass spectrometric study of the interactions betweencrown ethers and tetramethylammonium and tetramethylphosphoniumcations has revealed that, in solution, the complexes are based exclusivelyon C-H...O hydrogen bonds and that formation of the complexes with(CH3)4N

þ is favoured over formation of the complexes with (CH3)4Pþ (the

latter can be favoured for larger benzo-crown ethers when a solvent of lowpolarity is used, as a result of the participation of cation-p interactions).Moreover, in the gas phase, the complexes of crown ethers with the am-monium cation are essentially more stable than those with a phosphoniumcation.88

3 P-Ylides (phosphoranes)

3.1 Preparation

The well-known approach to functionalized phosphorus ylides based onthe three-component reactions of triphenylphosphine (TPP), dialkyl acet-ylenedicarboxylates (DAAD) and various EH-nucleophiles (E=N, O, S, C)stabilizing by protonation a reactive intermediate generated from thereaction of TPP and DAAD followed by addition of a conjugated base to thevinyltriphenylphosphonium salt formed, has continued to find application.When 2-bromoacetamide was used as a nucleophile in this reaction, a-amidophosphorus ylides (52) were formed, even despite the high reactivity of P(III)atom of phosphines towards alkyl halides and a-halocarbonyl compounds.89

Ethyl phenylcarbamate reacted in a similar way ((52), Y=OEt). The otherseries of stable a-amido phosphorus ylides (53) was produced from the abovereaction with 1-benzylidene-2-phenylhydrazines.90 The reaction of TPP,

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DAAD and a range of N–H, C–H or S–H acids, such as 2-thiazoline-2-thiol,2-benzoxazolinone, pyrrole-2-carboxaldehyde, benzotriazole, 5-methylben-zotriazole, 5-chlorobenzo-triazole, diethylmalonate, and acetylacetone to givethe corresponding ylides (54), was shown to occur in water as a sole mediumin the presence of polyethyleneglycol (PEG), b-cyclodextrin (b-CD), glycerine(Gly) or ethyleneglycol (EG), thus minimizing the cost operational hazardsperforming the reaction under environmentally benign conditions.91 Underthese conditions the reaction of 1,3-dimethylbarbituric or Meldrum’s acidresulted in the 1,4-diionic products (55).

OR

O

PPh3

NPh

RO

O

Y

O

R = Me, EtY=CH2Br, OEt

OR

O

PPh3

NPh

RO

O

NR1

R2

R1, R2 = H, Cl, F, NO2

OR

O

PPh3

RO

O

GOO

G = -N(CH3)-C(O)-N(CH3)-,-O-C(CH3)2-O-

NN

NR1

N

OO

R1=H, Cl, Me

N

SS

R2

O O

R2NCHO

OR

O

PPh3

Nu

RO

O

Nu =, ,

R2 = OEt, Me

(52) )45()35( (55)

Note that highly functionalized phosphorus ylides derived from the three-component reaction exist in solutions as a mixture of Z- and E-isomers ofthe corresponding zwitterionic species (56).The slow rotation about thepartial double bond in (E)-3 and (Z)-3 geometrical isomers on the NMRtimescale at room temperature allows an estimate of their mole ratio atequilibrium. For the zwitterionic salt of dimethyl 2(N-2-methylindole-1-yl)-3-(triphenylphosphoranylidene)butandioate (57) obtained via the abovestrategy from TPP, DAAD and 2-methylindole, a series of separatedynamic 1H NMR effects at different temperatures were reported. The effectswere attributed to restricted rotation around the heteroaryl–carbon andcarbon–carbon single bonds and also around carbon–carbon double bond.The rotational energy barriers (DG*) for the interconversion of rotationalisomers were evaluated as 55.33, 49.91 and 70.16� 2 kJ mol� 1, respectively.92

Ph3P

COOR

Nu

R=Me, Et

NCH3

Ph3P O

OMeMeOOC

O

OR

Ph3P

COOR

Nu O

OR

E-(56) Z-(56) (57)

Among the other developed approaches to novel P-ylides, the synthesis ofa-sulfanyl-a-phosphonyl phosphonium ylides (58) in quantitative yields viathe addition of two equivalents of trialkylphosphites to phosphonodithio-formates should be mentioned. The subsequent reaction of these ylides withalkyl or benzyl halides gives stabilized sulfonium ylides (59) while theirheating (18-150 h, 110 oC) leads to a-sulfanyl methylene bis-phosphonatesthrough protonation–dealkylation intramolecular reactions.93 The synthesis

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of a stable and structurally-characterized sila-ylide (as a mixture of twodiastereomers (60a) and (60b)) was accomplished via the reaction of aracemic 2-phosphinoenamine with magnesium in THF at room temperature.Interestingly, the reactivity of the sila-ylide towards aldehydes (Wittigolefination) was found to be similar to that of classical phosphonium ylides.94

P

SR2

P(OR1)3

OR1OR1O

R1 = Et, R2 = Me, CD3, R3= Me, Bn, CD3R1= iPr, R2 = Me

P

S

OR1OR1O

P

R3R2

OR1

OOR1

R2P

N

Si

Pri

iPr R2P

N

Si Ph

Pri

iPr

Ph 60a: 60b = 85:15

R2P = PN

NiPr

iPr

)a06()95()85( (60b)

Some papers pay special attention to the P-ylide structures. Thus, the abinitio conformational analysis of diester-stabilized ylides Ph3P=C(COOR)2(R=Me, Et, iPr, tBu) has revealed that conformations of diesters differ,depending on the nature of alkoxy groups: the acyl oxygen of the methyland ethyl ester group have syn-conformation, whereas in the case of abulkier alkoxy group (isopropoxy or t-butoxy) it is oriented towardsphosphorus (anti-), being in agreement with X-ray crystallographic evi-dence. Hence, small changes in the alkyl groups may change the conform-ation in the solid, and possibly also in solution, but rotational barriers forinterconversion of conformers should not be large. In fact, in solution,sharp signals are observed in the 1H and 13C NMR spectra due to the rapidinterconversion of conformers.95

Ph3POR

O

OR1

O

Ph3POR

O

R1OO

Ph3P

ROO

R1OO

syn-syn syn-anti anti-anti

Thermodynamic stabilities of ylides are known to be measured by theease of carbanion formation through the removal of a proton from theirprecursors. A Chinese research group has now performed the calculationson about 80 experimentally-characterized N-, P-, and S-ylide precursors anddeveloped an extensive scale of ylide thermodynamic stability that may findapplications in synthetic organic chemistry. This theoretical protocol canreliably predict the pKa values of diverse structurally unrelated ylideprecursors in DMSO with an error bar of ca. 1.6-1.9 pKa units.96

3.2 Reactions

3.2.1 Wittig reaction. The term ‘phosphorus ylide’ is indissolubly linkedwith the Wittig reaction being, along with the related Horner-Wadsworth-Emmons olefination, probably the best known examples of the use of or-ganophosphorus reactants in preparation of organic compounds and as oneof the most popular methods for C-C bond formation. Consequently, theWittig reaction of different P-ylides presents the traditional tool for the

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target synthesis of olefins, including biologically active ones, without af-fecting other functional groups. The importance of Wittig-type chemistry inbiochemistry and medicinal chemistry has been emphasized in reviews ofadvances in solution- and solid-phase synthesis of natural product-likelibraries97 and synthetic approaches and different applications of C-nu-cleosides.98 Note that phosphoryl-substituted carbanions are known to bemore reactive that the phosphorus ylides. For the first time a quantitativecomparison of these two classes of compounds based on the developednucleophilicity scale has been performed by R. Appel et al.99 Ph2PO- and(EtO)2PO-substituted carbanions were found to show similar reactivitiestoward Michael acceptors, which are 104-105 times higher than those ofanalogously substituted phosphorus ylides. The relative reactivities of thesenucleophiles toward benzaldehydes differ significantly from those towardcarbocations and Michael acceptors, in accordance with a concerted [2þ 2]cycloaddition being the initial step of these olefination reactions. Further-more, a similar conclusion was reached on the basis of comparison ofequilibrium acidities of diethoxyphosphoryl-substituted toluene, acetoni-trile, and ethyl acetate with the related ylides bearing triphenylpho-sphonium group. As the equilibrium acidity of these substrates increased by15.5, 14.9, and 10.9 pK units, respectively, for the introduction of ana-P(O)(OEt)2 and by 25.6, 24.4, and 21.0 pK units, repectively, for theintroduction of an a-PþPh3 group, the carbanions derived from phospho-nates (Horner-Wadsworth-Emmons reagents) are about 10 pK units morebasic (or nucleophilic) than those derived from the corresponding triphe-nylphosphonium ylides (Wittig reagents). However, both a-P(O)(OEt)2 anda-PþPh3 groups have negligible effects on the adjacent C-H bond dissoci-ation enthalpies, indicating that there is no resonance delocalization into the3d vacant orbitals of phosphorus and that their acidifying effects areexclusively associated with the field/inductive (electrostatic) and polariz-ability effects.100 It should be noted that the stereoselectivity of olefination isoften better for the standard Wittig reaction compared with that for theparticipation of HWE phosphonates.101

The typical Wittig reaction, using either preformed ylides or thosegenerated in situ from the corresponding phosphonium salts, was appliedfor construction of double bond in the total synthesis of Resolvin E1 (RvE1,an endogenous mediator to resolve inflammation),102 the polycyclicnatural product Nitidine,103 in the asymmetric total synthesis of pyranicin(a member of the annonaceous acetogenin family of natural products, beingamong the most powerful known inhibitors of mitochondrial complex I(NADH-ubiquinone oxidoreductase) in both mammalian and insectelectron transport systems),104 and that of (-)-Acylfulvene and (-)-Iroful-ven.105 This approach for double bond construction was also used as one ofthe key steps in the synthesis of enantiomerically pure eight members of thecyclooctanose family of carbasugars,106 beetle pheromones (R)-g-capro-lactone and (S)-japonilure and the hydroxylated g-lactone L-factor from2,3-O-isopropylidene-D- or L-erythrose,107 in the asymmetric synthesisof a decahydrofluorene tricyclic structure possessing eight stereogeniccenters and key features of the hirsutellone class of antitubercular naturalproducts,108 and 18-nor, 21-nor and 18,21-dinor analogs of (20S)-1a,

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25-dihydroxy-2-methylene-19-norvitamin D3,109 as well as for the con-struction of bicyclic analogues of monoterpene alkaloids belonging to thekinabalurine, incarvilline, and skytanthine families of natural products.110

Construction of key phenanthrene intermediates by a Suzuki coupling-Wittig olefination-ring-closing metathesis sequence provided a convergentand flexible approach to the hasubanan alkaloids (hasubanonine, runanine,and aknadinine).111 In the first synthesis of 4-F3 t-Neuroprostane and its 4-epimer, the E-selective HWE reaction and Z-selective Wittig olefinationwere used as key steps for the introduction of two unsaturated side chainsinto the chiral polyfunctional cyclopentane.112

In some of the above cases the commercially available phosphorus ylidesor phosphonium salts as ylide precursors were employed while, in somecases, a target design of a phosphonium salt or ylide was required. Thus,the chiral salt (-)-(61) was used in the synthesis of hemi-phorboxazoleanalogues,113 salts (62), derived from chloromethylated thieno[3,4-d]-1,3-dithiole-2-one, used as the starting substrates in the synthesis of conjugatedtrithienylenevinylene compounds bearing dithiocarbonate groups,114 theylide derived from the salt (63) was used (1.7:1 E/Z selectivity) in theenantioselective total synthesis of (-)-napyradiomycin A1,115 while the ylidegenerated from salt (64) was used in the total synthesis of ‘‘Danicalipin A’’,the major chlorosulfolipid from Ochromonas danica.116 The Wittig reactionof phosphonium bromide (65) was used as the key reaction step in thesynthesis of antitumor E-Stilstatin,117 while Wittig reactions of the salts (66)and (67) were applied for the synthesis of a few isomers of dietary carot-enoid lutein and all eight stereoisomers of lutein labeled with carbon-13for metabolic studies.118 Upadhyay and Kumar described a novel one-potsynthesis of coumarins via intramolecular Wittig cyclization of the inter-mediate generated from the reaction of phenolic compounds containingortho-carbonyl group and triphenyl(a-carboxymethylene)phosphorane

NN

OPh3P

PBu3 O

O

O

OBPS

Cl

(-)-61

S

SS

O

CH2PPh3Cl Me

PPh3 Me

Me

I

Ph3PCl Cl

OTBS7

I

(62)

PPh3BrH3CO

TBDMSO

OCH3

PPh3Cl

HO3

PPh3Cl

AcO3

6

ClO

Ph3PPPh3Br

OTBS OPMB

(64)

(65) (66)(67)

(68) (69) (70)

R

R = H, CH2PPh3Cl

(63)

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imidazolide (68).119 The latter was prepared by the reaction ofcarbonyl diimidazole and methylenetriphenyl phosphorane, Ph3P=CH2,generated from the corresponding phosphonium salt. A smooth Wittigreaction of the phosphorus ylide (69) derived from 1,3-dichloroacetoneand triphenylphosphine (THF, reflux, 24 h, 98% yield), and protectedindolecarboxaldehyde in refluxing MeOH was used in the practicalsynthesis of the biologically active cycloanthranilylproline derivativesfuligocandines A and B.120

For subsequent introduction of a series of double bonds the Wittig ole-fination can be used more than once. For example, preparation of func-tionalized [5]- and [6]-carbohelicenes required two subseqent Wittigreactions.121 The Wittig reaction, followed by Horner-Wadsworth-Emmonsolefination, was used in the synthesis of phosphonium salt (70) subsequentWittig olefination of which with a substituted pyrancarboxaldehydeprovided the PMB-protected interemediate (Z)-alkene in 86% yield andas a single geometric isomer. The latter was further used in the synthesis of a35-membered library of stereoisomers of bistramide A.122 Furthermore,Wittig homologation of a substituted benzaldehyde with participation ofPh3P=CHOMe generated in situ was used in the enantioselective totalsynthesis of (-)-Acutumine,123 a combination of Wittig homologation andWittig olefination was applied in the total synthesis of integric acid.124 Thesynthesis of glycolipids and mimetics containing either a-glucuronic acidor a-galacturonic acid residues using ylides generated in situ from thelong chain phosphonium salt [Ph3PCH2C13H27]Br,

125 that of glucosidaseinhibitors schulzeines B and C with participation of the phosphonium salt[Ph3P(CH2)10COOBn]Br126 as well as the facile synthesis of a,b-unsaturatedamides RCH=CHC(O)NEt2 (R=Ph, 4-O2N-C6H4, 2-O2N-C6H4, 4-CH3-C6H4, 4-ClC6H4, 2-CH3OC6H4, C4H9 etc.) in good yields with highE-selectivity, starting from preformed carbamoylmethylenetriphenyl-phosphorane ylide,127 continue the long list of publications where thistask-oriented reaction was used.

Wide application of the Wittig reaction has resulted in a search for newconditions allowing improvements in the yield or stereoselectivity of theprocess. The solid-phase Wittig reaction starting from the reaction ofpolymer-supported triphenylphosphine (PS-TPP) with bromoacetophe-nones and subsequent ylide (71) generation in the presence of a base, wasapplied in the synthesis of hybrid vinylthio-, vinylsulfinyl-, vinylsulfonyl-,and vinylketobenzofuroxans, developed as anti-trypanosomatid agentsagainst Trypanosoma cruzi and Leishmania spp.128 Alonso et al. havefound that nickel nanoparticles (NiNPs), readily prepared from NiCl2,lithium metal, and a catalytic amount of DTBB (4,4-di-tert-butylbiphenyl)in THF, are able to promote a Wittig type olefination of primary alcoholswith phosphorus ylides generated in situ from the corresponding phos-phonium salts with nBuLi or with lithium metal. The NiNPs were shown tobe catalytically superior to other forms of nickel in this reaction which wasespecially efficient for the synthesis of stilbenes using benzyl alcohols assemistabilised benzylidenetriphenylphosphorane partners, e.g., (72), andallowed a novel synthesis of resveratrol, DMU-212 and analogues based onthe above strategy.129,130 As the pursuit of green and environmentally

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benign synthetic protocols has begun to delve into the organophosphorusarea, successful examples of a Wittig approach performed under aqueousconditions have been reported. Thus, a direct synthesis of 1,3-dienes and1,3,5-trienes from the reaction of semi-stabilized ylides, derived in situ fromtrialkylallylphosphonium salts, and a range of saturated and unsaturatedaldehydes was performed in water as a solvent, employing sodiumhydroxide as a base.Ylide formationoccurs exclusively throughdeprotonationat the allylic position and the water-soluble phosphine oxide side product isremoved simply by aqueous partitioning of the organic products. The reactionis very chemoselective forolefinationunder conditionswhere competinghomo-aldol or Cannizaro disproportionation reactions might be anticipated.131

Similarly, the chemoselective formation of trialkyl(benzylidene) ylides inwater and theirWittig reactionwith aromatic and aliphatic aldehydes providesa practical and stereoselective route to valuable (E)-stilbenes and alkenes.132

Moreover, the method allows a gram-scale synthesis of the anticancer agentDMU-212 utilizing no organic solvent at any stage.

The Wittig olefination can also be combined with other reactions in so-called tandem or cascade reactions, performed as one-pot processes, whichhave undoubted advantages in the effective synthesis of organic compounds.Therefore, a one-pot cascade transylidation–olefination sequence the com-prising formation of linear phosphonium salts (73) based on protected ester-substituted aminoethylbromides, their mild cyclization after deprotonation(tBuOK, toluene, reflux) to afford b-keto-ylides (74), followed by the Wittigreaction in CH3CN, afforded a number of 3-alkylidene-piperidin-4-oneswith diverse C-5 substitution patterns.133 However, only tributylsubstitutedphosphorus ylides (74) provided the olefination products due to its highernucleophilicity, while the triphenylphosphorus analogs were unreactive. Inthe other cascade synthesis, the one-pot Wittig olefination and enereaction of the phosphorane (75) with glyoxalic acid gave the cis fusedpyrrolidine skeleton of kainic acid.134 The starting phosphorane was obtainedon deprotonation of the corresponding phosphonium salt obtained via amultistep procedure comprising N-alkylation of benzylamine with prenylbromide, treatment of monoalkylated benzylamine with bromoacetyl

NBn PR3

COOMe

NBn

O

PR3

R=Ph, Bu, Cy R = Ph, Bu

Ph3P

NO

R

R= C6H5CH2, 4-MeO-C6H4CH2

PPh Ph O

R

PPh3MeO

MeO

OMe

OMe

O

PAr2R

PAr2R

MeO

MeO

Ar = Ph, 3-MeO-C6H4, 3,5-tBu2-4-MeO-C6H2

R =

PPh2R

PPh2R

(R) (S)

(71) (72) (73) (74)

(75) )77()67(

Br

Br

Br

Br

Br

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bromide, and alkylation of PPh3. Zhou and coworkers reported thefirst example of the asymmetric tandem ylide formation-Michael addition–olefination reaction of phosphonium salts (76) and (77), based on (R)-2,2’-bis(diphenylphosphino)-1,10-biphenyl (BIPHEP) and (S)-BINAP, respect-ively, and a,b-unsaturated ketones to give cyclohexa-1,3-dienes with good tohigh ee in good yields. Depending on the structure of the starting phospho-nium salt, both enantiomers of the final product were provided.135

A recent review on the uses of bromodimethylsulfonium bromide([Me2S

þBr]Br� , BDMS) in organic synthesis opened a subject of BDMSapplication for the one-pot synthesis of a-haloacrylates from stabilizedphosphorus ylides and aldehydes in high Z/E ratios, together with otherreactions.136 The procedure is suggested to involve a rapid in situ formationof mixed phosphonium-sulfonium ylides followed by conversion into a-halo-phosphonium ylide, e.g.,, Ph3P=C(Br)COOR, and subsequent Wittigreaction.

3.2.2 Miscellaneous reactions. Sweeney has attempted to attract atten-tion to the area of sigmatropic rearrangements of ‘onium’ ylides, includingphosphorus ones, and its still under-employed capacities in current organicchemistry.137 Nevertheless, though in theory a feasible transformation, re-arrangement reactions of phosphonium ylides have only been sparsely re-ported. The reaction of allylic phosphoranes (79) (both obtained in situ fromthe corresponding phosphonium salts (78), or preformed) with iron por-phyrin carbenoids, e.g., formed from tetra(4-chlorophenyl)porphyrin ironchloride [Fe(TCP)Cl] and methyl diazoacetate, proceeds as a formal carbe-noid insertion reaction into olefinic C-H bonds. The mechanistic investigationshowed that the insertion involves cyclopropanation of the allylic ylide withthe iron carbenoid followed by ring opening of the resulting cyclopropaneylide (80) and subsequent formation of the ylide (81). On the basis of thisobservation, a one-pot reaction of a tributylphosphine-derived ylide andaldehydes in the presence of [Fe(TCP)Cl] has been developed, providing easyaccess to 1,1,4-trisubstituted 1,3-butadienes with high stereoselectivity undermild conditions.138

R3P COOMe

COOMe

R3PCOOMe

H COOMe

R3P COOMe

R3P COOMeBrLiHMDS, PhMe

COOMe(PCT)Fe(78)

(79) (80) (81)

Addition reactions of (1-methoxyalkyl)triphenylphosphonium ylides,derived from the corresponding phosphonium salts (82) and n-BuLi, toaldehydes at � 78 oC followed by quenching the reaction mixture withaqueous NH4Cl at the same temperature afforded a-hydroxyketones insteadof the expected enol ethers.139 This is the first example of phosphoniumylides acting as an acyl anion equivalent. Flash vacuum pyrolysis (FVP) in aconventional flow system at 10� 1–10� 2 Torr of stabilised ylides (83) and(84), prepared in a few steps from 2-(methylthio)nicotinic acid, give

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products containing previously unknown naphtho-, phenanthro-, ben-zothieno, and benzofuro-fused thieno[2,3-b]pyridine ring systems.140

Ph3P R

OMe

X

R = Me, (CH2)3OTBDPS, (CH2)4CH3

X = Cl, BF4

N

R

O PPh3

SMe N

Ph3P O

SMe

Ar

R = Et, Ph, 2-MeS-C6H4, 2-MeOC6H4 Ar = Ph, 2-thienyl, 2-furyl, 1-naphthyl

(82) (83) (84)

O

NOH

Ph3P

YPh

Y = CN, COMe, C(O)H, COOR

Ph3P

PhI

O

RBF4

PPhPh

R

R1 R2OC

NPh3P

R R1

R=OEt, Ph R1 = H, R2 = Ph, 4-CH3OC6H4, C8H17, c-C3H5,

R1 = Ph, R2 = Ph2CH, CPhCR1 + R2 = (CH2)6

R = OEt, R1 = MeR = OMe, R1= EtR = Ph, R1 = Ph, 4-Py, NEt2

R = Me, Et

(85) (86) )88()78(

BF4

The reaction of 2-phenyl-5-(4H)-oxazolone and its 4-benzylidenederivative with oxovinylidenetriphenylphosphorane Ph3P=C=C=Oafforded 2-phenylfuro[3,2-d][1,3]oxazol-5-(6H)-one and 2,7-diphenyl-5H-pyrano[3,2-d][1,3]oxazol-5-one along with triphenylphosphine. Alter-natively, oxazolone reacting with stabilized ylides Ph3P=CH-Y(Y=COOMe, COOEt, CN, COMe, CHO) gave the new cyclic phosphor-anes (85).141 Zefirov et al. demonstrated that the thermal pseudocy-cloaddition of the mixed phosphonium-iodonium ylides (86) with aliphaticnitriles in the presence of DMAD surprisingly resulted in scarce phospho-nium-substituted oxazoles (87). More interestingly, under UV irradiationconditions (Hg lamp) this cycloaddition leads to oxazoles (87) with goodyields in the absence of DMAD.142 Furthermore, a photochemical reactionof the phosphonium-iodonium ylides (86) with acetylenes afforded l5-phosphinolines (88) in 35-80% yields, belonging to a rare class of phos-phorus heterocycles hardly accessible by other methods.143 In the reactionwith internal acetylenes, the products were formed as a mixture of twoisomers which were not separated. Hence, the irradiation of ylides (86) withUV light generates a highly electrophilic intermediate which can be trappedby nucleophilic alkynes to yield a variety of phosphorus heterocycles.

3.3 Coordination properties

Atropochiral NHC-phosphonium ylides obtained from the correspondingbistriflate dicationic phosphonium salt (89) bearing the naphthyl-benzimi-dazolyl core, have been revealed as strongly s-donor C,C-chelating ligandsof transition metals. Depending on the reaction conditions, they can acteither as a monodentate (through the carbene center as in the complex (90))or a bidentate ligand (forming coordination bonds through the carbene andthe ylide centers as in the complex (91)). In the last case, the authors suc-ceeded to separate the diastereoisomeric complexes (R,R)-(91) and (R,S)-(91) by fractional crystallisation. Hydrochloric treatment of either

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diastereoisomer of (91) was found to keep intact the two carbon–palladiumbonds, affording the corresponding enantiomeric b-zwitterionic NHC-ylidepalladate complexes (92).144 The reaction of a mixed phosphine–phospho-nium ylide, PPh2CH2(Ph2)P=C(H)C(O)Ph with mercury(II) halides yieldedthe P,C-chelate complexes (93).145 As one can expect, in the reactions of therelated phosphine–phosphonium salt, [PPh2CH2P

þPh2CH2COPh]Br� ,with mercury(II) halides the salt serves as a P-monodentate ligand to givezwitterionic mixed halogen mercurates (94).146 Cationic rhodium Z2-com-plex (95) of a chelating semistabilized phosphino-phosphonium sulfinyl-ylide ligand can be obtained in inverse ratios (90:10 or 10 : 90) of (RC) and(SC) epimeric forms depending on the kinetic or thermodynamic conditionsused in the complexation reaction. Deprotonation of (95) afforded theneutral complex (96) of the corresponding yldiide ligand, being unstable inair and decomposing even at low temperature under an inert atmosphere.Despite such limited stability of the yldiide complex (96), its structure wasascertained by ESI MS and multinuclear 1H, 31P, 13C, and 103Rh NMRspectroscopy. According to ELF and AIM topological analyses, the phos-phonium sulfinylyldiide can be regarded as a tris-zwitteranionic bisylide(Ar3P

þ -C2� -Sþ (-O-)p-Tol).147

Ph2P P Ph

OPh

Ph

HgX

X Br

X=Cl, Br

N

N

Me

PPh2

Me

2OTf N

N

Me

PPh2

Me

OTf

Pd NCl

N

N

Me

PPh2

OTfPd N

CH2

N

N

Me

PPh2

Pd Cl

CH2

Cl

(R)- or (S)-(92)

PRh(cod)

CPPhPh

PhPh

H

S Op-Tol

PF6

PRh(cod)

CPPhPh

PhPh

S O

p-Tol

(89) (90) (91)

PPh2P

Hg

PhPh

PhO

XX

X=Cl, Br, I

)49()39( (95) (96)

The known ylide-sulfonium salt [Ph3P=CHC(O)CH2SMe2]Br was foundto react with PdCl2(NCMe)2 in the presence of NEt3 to give selectively themeso diastereoisomer (RS/SR) of cis-palladium complex (97). In contrast,the related reaction of the ylide-sulfide [Ph3P=CHC(O)CH2SMe] followedby the treatment with Ph3P led to the k2-C,C complex with anionic ylide-methanide ligand [Ph3PCHC(O)CHSMe]� exclusively in the RR/SS con-figurations (d,l pair). Otherwise, the same complex could be obtained in thereaction of the ylide-sulfide with PdCl2(NCMe)2 in MeOH with subsequentdeprotonation at the methylene group in the intermediate 5-memberedcomplex with chelate k2-C,S ligand. Complex (97) can be easily converted,with retaining of the bis-ylide unit, into the related complexes differingin the additional ligands at the Pd atom. Refluxing one of thesecomplexes, namely [PdCl(PPh3)-[Ph3PCHC(O)CHSMe2-k-C,C]]ClO4, pro-motes orthopalladation of the phenyl ring at the ylidic phosphorus atom to

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afford monopalladacycle (98).148 Density functional theory (DFT) andBader’s Atoms in Molecules (AIM) studies on S-ylides, mixed P-S bis-ylides, and the corresponding Pd complexes have been performed.Unusually for the classical soft metals, the O-Pd(II) bonded complex (99),with oxygen-coordinated ylide, was obtained from the reaction of [4-methoxybenzoyl)methylene]triphenylphosphorane with a cationic cyclo-palladated precursor. O-Coordination of the ylide and the cisoid structureof the complex were confirmed by single-crystal X-ray analyses and IRspectroscopy.149

PdNH2

OPy

H

PPh3

MeO

CF3SO3

Ph3PC

Ph3PAg

PPh3C

PPh3

Ph3PC

Ph3PAg

PPh3C

PPh3

H

H

+

3+

Pd

SMe2

HCl Cl

O

Ph3P

HP

PdCl PPh3

H

Me2S

OPh Ph

(97) (98) (99)

(100)

(101)

Wright et al. described the first structurally characterized dilithiatedphosphorylide being a stable source of a tridentate [PhP(CH2)3]2

� ligand.The stable in storage lithium salt [Li2{PhP(CH2)3}3 2thf]2 was obtained viadeprotonation of [PhP(CH3)3]

þ I� with three equivalents of tBuLi. Thelow-temperature crystal structure analysis of this complex has revealed thatit consists of a dimer, comprised of two symmetry-related, inverted um-brella-shaped [PhP(CH2)3]2

� dianions held together by four, thf-solvatedLiþ cations.150 The double ylide C(PPh3)2 having two lone pairs of freeelectrons in reaction with silver salts AgX (X=Cl, BF4) in THF affordedthe cationic complex (100)þ in which the ligand acted as a two electrondonor. The reaction of the salt (HC(PPh3)2)BF4 with AgBF4 led to thecomplex (101)3þ , where the ligands provide four electrons. In both com-plexes a linear C–Ag–C array is achieved as was elucidated by X-rayanalyses.151

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